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Bo Wu,1,* Bing Wan,2,* Shu-Ting Lu,1 Kai Deng,3 Xiao-Qi Li,1 Bao-Lin Wu,1 Yu-Shuang Li,1 Ru-Fang Liao,1 Shi-Wen Huang,3 Hai-Bo Xu1,2 1Department of Radiology, Zhongnan Hospital of Wuhan University, 2Department of Radiology, Union Hospital of Tongji Medical College, Huazhong University of Science and Technology, 3Department of Chemistry, Key Laboratory of Biomedical Polymers, Ministry of Education, Wuhan University, Wuhan, People’s Republic of China *These authors contributed equally to this work Abstract: The major challenge in current clinic contrast agents (CAs) and chemotherapy is the poor tumor selectivity and response. Based on the self-quench property of IR820 at high concentrations, and different contrast effect ability of Gd-DOTA between inner and outer of liposome, we developed “bomb-like” light-triggered CAs (LTCAs) for enhanced CT/MRI/FI multimodal imaging, which can improve the signal-to-noise ratio of tumor tissue specifically. IR820, Iohexol and Gd-chelates were firstly encapsulated into the thermal-sensitive nanocarrier with a high concentration. This will result in protection and fluorescence quenching. Then, the release of CAs was triggered by near-infrared (NIR) light laser irradiation, which will lead to fluorescence and MRI activation and enable imaging of inflammation. In vitro and in vivo experiments demonstrated that LTCAs with 808 nm laser irradiation have shorter T1 relaxation time in MRI and stronger intensity in FI compared to those without irradiation. Additionally, due to the high photothermal conversion efficiency of IR820, the injection of LTCAs was demonstrated to completely inhibit C6 tumor growth in nude mice up to 17 days after NIR laser irradiation. The results indicate that the LTCAs can serve as a promising platform for NIR-activated multimodal imaging and photothermal therapy. Keywords: light triggered, near-infrared light, tumor-specific, multimodal imaging, photothermal therapy, contrast agents

Objective: To explore clinical efficacy of congenital brachymetatarsia with immediate metatarsal lengthening., Methods: From March 2015 to December 2020, 7 patients with brachymetatarsia were treated, including 6 females and 1 male;aged range from 18 to 30 years old;there were 5 patients with metatarsal microsomia on one foot, 2 patients with metatarsal microsomia on the first and fourth right foot, and immediate extension of metatarsal microsomia on the first and fourth right foot;two patients were short metatarsal bones of both feet. The length of short metatarsal bone, length of normal metatarsal bone, distance of short metatarsal bone and healing of bone graft were observed before and 12 months after operation. American Orthopaedic Foot and Ankle Society (AOFAS) scores were used to evaluate clinical efficacy and observe complications., Results: Seven patients were followed up for 12 to 24 months. All metatarsal bones were extended to satisfactory length and bone graft were healed completely. Metatarsal length and shortening distance were improved from 3.55 to 5.90 cm and 0.77 to 1.46 cm before operation to 4.31 to 6.87 cm and 0.04 to 0.57 cm at 12 months after operation. Postoperative X-ray of the affected foot at 12 months showed bone healing was achieved between metatarsal bone and bone graft in 7 patients, and the parabolic shape of the distal metatarsal bone recovered after operation. AOFAS scores improved from 40 to 70 before operation to 88 to 95 points at 12 months after operation, and 6 patients were excellent and 1 good., Conclusion: Immediate extension of metatarsal bone for congenital brachymetatarsia, the transplanted bone grew well during the process of bone grafting healing, the occurrence of bone nonunion was reduced, the short metatarsal bone was restored to a satisfactory length, and the toe function restored well.

This study aims to evaluate the feasibility, safety, and effectiveness of an optimized treatment approach for complex renal calculi, utilizing visual needle nephroscopy in conjunction with standard PCNL and holmium YAG laser. We collected data from 62 patients diagnosed with complex kidney stones who underwent this combined procedure using the visual needle nephroscope (Needle-perc ® , Youcare Tech, Wuhan, China). The percutaneous nephroscopic working channel was established by visual needle nephroscope, and the primary channel was expanded to 20 F to treat most of the main body of the calculi with a 550 μm holmium laser fiber. Visual needle nephroscope was used to locate the renal calyx where the residual calculi were located for precise puncture as a secondary channel, and the residual stones were treated by a 200 μm holmium laser fiber. Clinical data were collected, and intraoperative variables, postoperative complications and outcomes were assessed. All 62 patients successfully completed the operation without severe complications. The S.T.O.N.E. score of 62 patients before operation was 10.5 ± 0.9 points and above, of which the N score was more than 2 points. The average operation time was (65.5 ± 12.7) minutes, and the average hospital stay was (7.3 ± 2.1) days. After operation, 2 patients developed a fever, which improved after symptomatic treatment by intravenous antibiotics. 4 patients had clinically significant residual fragments, and the stone-free rate of primary operation was 93.5% (58/62). The optimized operation for the treatment of complex renal calculi based on standard PCNL combined with visual needle nephroscope by holmium YAG laser has good feasibility, safety and effectiveness., Competing Interests: Declarations. Ethical approval and consent to participate: The experimental protocol was established according to the ethical guidelines of the Helsinki Declaration and was approved by the Human Ethics Committee of Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology. Written informed consent was obtained from individual or guardian participants. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

A concise enantioselective total synthesis of (-)-daphenylline, a hexacyclic Daphniphyllum alkaloid with a unique benzene ring, was achieved in 14 steps. The synthesis commences with two chiral stereocenters, C2 and C18, readily installed via Carreira's Ir/amine dual-catalyzed allylation. The allylic bridgehead amine 6 was rapidly prepared through Wickens' photoredox-catalyzed hydrocarboxylation of olefin and CuBr 2 -catalyzed α-amination of ketone. The tetracycle 4 was formed via Pd-catalyzed reductive Heck reaction or, more concisely, by Krische's Rh-catalyzed reductive 1,6-enyne cyclization. In this synthesis, newly reported Wickens' photoredox-catalyzed hydrocarboxylation was used twice, and Friedel-Crafts acylation thrice.

This case report describes a 47-year-old woman with systemic lupus erythematosus (SLE) complicated by Libman-Sacks endocarditis (LSE) who developed multiple organ dysfunction after mitral valve replacement surgery. The patient presented with a 5-day history of cough, sputum, and fever. Transthoracic echocardiography showed significant vegetations on the mitral valve. Biopsy was performed, and the pathological diagnosis was SLE complicated by LSE. After the mitral valve replacement surgery, the patient developed clinical manifestations of hepatic and renal dysfunction, cardiopulmonary failure, oliguria, and shock. The clinical symptoms significantly improved after administration of mechanical ventilation, continuous renal replacement therapy, plasma exchange, anti-inflammatory and anti-infection treatments, immunomodulatory and immunosuppressive therapies, and low-molecular-weight heparin anticoagulation. Multiple organ dysfunction after mitral valve replacement in patients with SLE complicated by LSE has rarely been reported. This report discusses the clinical manifestations, pathogenesis, and treatment of this severe complication. We hope the sharing of our experience in this case will provide a clinical basis for the treatment of severe multiple organ dysfunction after mitral valve replacement in patients with SLE complicated by LSE.

Background: Human microbiome dysbiosis is related to various human diseases, and identifying robust and consistent biomarkers that apply in different populations is a key challenge. This challenge arises when identifying key microbial markers of childhood caries., Methods: We analyzed unstimulated saliva and supragingival plaque samples from children of different ages and sexes, performed 16S rRNA gene sequencing, and sought to identify whether consistent markers exist among subpopulations by using a multivariate linear regression model., Results: We found that Acinetobacter and Clostridiales bacterial taxa were associated with caries in plaque and saliva, respectively, while Firmicutes and Clostridia were found in plaque isolated from children of different ages in preschool and school. These identified bacterial markers largely differ between different populations, leaving only Saccharibacteria as a significant caries-associated phylum in children. Saccharibacteria is a newly identified phylum, and our taxonomic assignment database could not be used to identify its specific genus., Conclusion: Our data indicated that, in a South China population, oral microbial signatures for dental caries show age and sex differences, but Saccharibacteria might be a consistent signal and worth further investigation, considering the lack of research on this microbe., Competing Interests: The authors declare that they have no competing interests., (© 2023 You et al.)

This study investigated the correlation between 3-Tesla magnetic resonance imaging (MRI) and 256 multiple-slice computed tomography (MSCT) or 2-dimensional echocardiography (ECHO) in evaluating left ventricle. Forty patients were retrospectively enrolled to undergo cardiac MSCT, 3-Tesla MRI and 2-dimensional ECHO within 1 week. The end-diastolic (EDV) and end-systolic volume (ESV), stroke volume (SV) and ejection fraction (EF) were analyzed and compared. MSCT was highly significantly correlated with MRI. Compared with MRI, MSCT slightly overestimated ESV for about 8.7 mL, but slightly underestimated EF and SV for about 6.8% and 5.8 mL, respectively. A high consistency existed between MSCT and MRI, with the 95% limit of agreement (-19.6, 25.4) mL for EDV, (-2.6,20.1) mL for ESV, (-28.3,16.6) mL for SV, and (-18.8%,5.1) % for EF. ECHO was also significantly correlated with MRI. The ECHO slightly underestimated the left ventricular function compared with MRI, with an underestimation of 9.4 mL for EDV, 3.5 mL for ESV, 5.8 mL for SV and 1.0% for EF. A wider agreement limit existed between MRI and ECHO. MSCT has a better correlation and agreement relationship with MRI parameters than 2-dimensional ECHO in assessing the left ventricle and may serve as a possible alternative to MRI., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

The main causes of damage to industrial machinery are aging, corrosion, and the wear of parts, which affect the accuracy of machinery and product precision. Identifying problems early and predicting the life cycle of a machine for early maintenance can avoid costly plant failures. Compared with other sensing and monitoring instruments, sound sensors are inexpensive, portable, and have less computational data. This paper proposed a machine tool life cycle model with noise reduction. The life cycle model uses Mel-Frequency Cepstral Coefficients (MFCC) to extract audio features. A Deep Neural Network (DNN) is used to understand the relationship between audio features and life cycle, and then determine the audio signal corresponding to the aging degree. The noise reduction model simulates the actual environment by adding noise and extracts features by Power Normalized Cepstral Coefficients (PNCC), and designs Mask as the DNN's learning target to eliminate the effect of noise. The effect of the denoising model is improved by 6.8% under Short-Time Objective Intelligibility (STOI). There is a 3.9% improvement under Perceptual Evaluation of Speech Quality (PESQ). The life cycle model accuracy before denoising is 76%. After adding the noise reduction system, the accuracy of the life cycle model is increased to 80%.

Background: Cardiac valve calcification (CVC) is an important risk factor for cardiovascular complications. However, limited data are available concerning the prevalence, clinical features and risk factors for CVC in end-stage kidney disease (ESKD) patients. In this study, we aimed to assess these parameters in Chinese ESKD patients receiving combination therapy with hemodialysis and hemodiafiltration., Methods: We conducted a cross-sectional study on 293 ESKD patients undergoing combination therapy of hemodialysis and hemodiafiltration at the First Affiliated Hospital of Chongqing Medical University from October 2014 to December 2015. CVC was evaluated via echocardiography., Results: ESKD patients with CVC had a higher prevalence of diabetes mellitus, aortic and/or coronary artery calcification, arrhythmia, heart failure and coronary heart disease; increased systolic, diastolic and pulse pressure; longer duration of hemodialysis and hypertension; reduced hemoglobin, albumin and high-density lipoprotein cholesterol levels; and increased serum calcium and calcium-phosphorus product levels compared with those without CVC. Logistic regression analysis showed that increased dialysis duration ( p  = 0.006, OR = 2.25), serum calcium levels ( p  = 0.046, OR = 2.04) and pulse pressure ( p  < 0.001, OR = 3.22), the presence of diabetes ( p  = 0.037, OR = 1.81) and decreased serum albumin levels ( p  = 0.047, OR = 0.54) were risk factors for CVC. The correlation analysis indicated a significantly increased CVCs prevalence with an increase prevalence of heart failure, aortic and coronary artery calcification., Conclusions: CVC represents a common complication and a danger signal for cardiovascular events in ESKD patients undergoing combination therapy of hemodialysis and hemodiafiltration. The presence of diabetes, increased pulse pressure, long dialysis duration, hypoalbuminemia and high serum calcium levels were independent risk factors for CVC.

Purpose: This preclinical study aimed to evaluate whether using transferred mosaic embryos (primarily selected by embryonic morphology assessment (EMA) and compared by the noninvasive preimplantation genetic testing for aneuploidy (niPGT-A) on cell-free DNA in blastocoel fluid (BF)) increases the rates of clinical pregnancies (CPs) and healthy live births (HLBs) and to investigate whether niPGT-A could provide valuable genetic information for the EMA-selected transferred mosaic embryos., Methods: This study collected 215 blastocyst culture samples and 182 BF samples. Cell-free DNA from the BF was amplified and examined by next-generation sequencing-based niPGT-A. All 182 patients underwent EMA. However, only 147 underwent in vitro fertilization and embryo transfer, and only 113 clinical outcomes were followed up. Comprehensive chromosome screening for the chorionic villus sampling of spontaneous miscarriages and noninvasive prenatal testing for ongoing pregnancies were also performed., Results: The implantation rate was 77.55% in 147 transferred high-quality embryos selected by EMA. Among 113 CPs, 16 led to spontaneous miscarriage (14.16%), and 97 resulted in HLBs (85.84%). According to the niPGT-A results for 113 patients with clinical outcomes, 80.4% had CP (euploid, 20.54%; single aneuploid, 1.79%; mosaic chromosome aneuploid and/or segmental aneuploid, 58.04%). Of all the mosaic aneuploids, 90.76% were false positive, transforming to euploid., Conclusions: Transferred EMA-selected embryos showed higher implantation rates. The niPGT-A of BF provided valuable genetic status ("-ploid") information, which helped reduce aneuploid-induced implantation failure and miscarriage, thereby increasing the CP and HLB rates. Additionally, majority of the transferred embryos with complex/chaotic mosaic aneuploid would likely develop HLBs., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: To investigate the effect of hypochloric acid on Escherichia coli biofilm and the clinical efficacy of hypochloric acid for wounds with Escherichia coli infection. Methods: One strain of Escherichia coli with the strongest bacterial biofilm forming ability among the strains isolated from specimens in 25 patients (16 males and 9 females, aged 32-67 years) from five clinical departments of the 940 th Hospital of the Joint Logistic Support Force was collected for the experimental study from September to December 2019. The Escherichia coli was cultured with hypochloric acid at 162.96, 81.48, 40.74, 20.37, 10.18, 5.09, 2.55, 1.27, 0.64, and 0.32 μg/mL respectively to screen the minimum bactericidal concentration (MBC) of hypochloric acid. The Escherichia coli was cultured with hypochloric acid at the screened MBC for 2, 5, 10, 20, 30, and 60 min respectively to screen the shortest bactericidal time of hypochloric acid. The biofilm formation of Escherichia coli was observed by scanning electron microscopy at 6, 12, 24, 48, 72, and 96 h of incubation, respectively. After 72 h of culture, hypochloric acid at 1, 2, 4, 8, and 16 times of MBC was respectively added to Escherichia coli to screen the minimum biofilm eradicate concentration (MBEC) of hypochloric acid against Escherichia coli. After hypochloric acid at 1, 2, 4, and 8 times of MBEC and sterile saline were respectively added to Escherichia coli for 10 min, the live/dead bacterial staining kit was used to detect the number of live and dead cells, with the rate of dead bacteria calculated (the number of samples was 5). From January to December 2020, 41 patients with infectious wounds meeting the inclusion criteria and admitted to the Department of Burns and Plastic Surgery of the 940 th Hospital of Joint Logistic Support Force of PLA were included into the prospective randomized controlled trial. The patients were divided into hypochloric acid group with 21 patients (13 males and 8 females, aged (46±14) years) and povidone iodine group with 20 patients (14 males and 6 females, aged (45±19) years) according to the random number table. Patients in the 2 groups were respectively dressed with sterile gauze soaked with hypochloric acid of 100 μg/mL and povidone iodine solution of 50 mg/mL with the dressings changed daily. Before the first dressing change and on the 10 th day of dressing change, tissue was taken from the wound and margin of the wound for culturing bacteria by agar culture method and quantifying the number of bacteria. The amount of wound exudate and granulation tissue growth were observed visually and scored before the first dressing change and on the 3 rd , 7 th , and 10 th days of dressing change. Data were statistically analyzed with one-way analysis of variance, Dunnett- t test, independent sample t test, Mann-Whitney U test, Wilcoxon signed-rank test, chi-square test, or Fisher's exact probability test. Results: The MBC of hypochloric acid against Escherichia coli was 10.18 μg/mL, and the shortest bactericidal time of hypochloric acid with MBC against Escherichia coli was 2 min. Escherichia coli was in a completely free state after 6 and 12 h of culture and gradually aggregated and adhered with the extension of culture time, forming a mature biofilm at 72 h of culture. The MBEC of hypochloric acid against Escherichia coli was 20.36 μg/mL. The Escherichia coli mortality rates after incubation with hypochloric acid at 1, 2, 4, and 8 times of MBEC for 10 min were significantly higher than that after incubation with sterile saline (with t values of 6.11, 25.04, 28.90, and 40.74, respectively, P <0.01). The amount of bacteria in the wound tissue of patients in hypochloric acid group on the 10 th day of dressing change was 2.61 (2.20, 3.30)×10 4 colony forming unit (CFU)/g, significantly less than 4.77 (2.18, 12.48)×10 4 CFU/g in povidone iodine group ( Z =2.06, P <0.05). The amounts of bacteria in the wound tissue of patients in hypochloric acid group and povidone iodine group on the 10 th day of dressing change were significantly less than 2.97 (2.90, 3.04)×10 6 and 2.97 (1.90, 7.95)×10 6 CFU/g before the first dressing change (with Z values of 4.02 and 3.92, respectively, P <0.01). The score of wound exudate amount of patients in hypochloric acid group on the 10 th day of dressing change was significantly lower than that in povidone iodine group ( Z =2.07, P <0.05). Compared with those before the first dressing change, the scores of wound exudate amount of patients in hypochloric acid group on the 7 th and 10 th days of dressing change were significantly decreased (with Z values of -3.99 and -4.12, respectively, P <0.01), and the scores of wound exudate amount of patients in povidone iodine group on the 7 th and 10 th days of dressing change were significantly decreased (with Z values of -3.54 and -3.93, respectively, P <0.01). The score of wound granulation tissue growth of patients in hypochloric acid group on the 10 th day of dressing change was significantly higher than that in povidone iodine group ( Z =2.02, P <0.05). Compared with those before the first dressing change, the scores of wound granulation tissue growth of patients in hypochloric acid group on the 7 th and 10 th days of dressing change were significantly increased (with Z values of -3.13 and -3.67, respectively, P <0.01), and the scores of wound granulation tissue growth of patients in povidone iodine group on the 7 th and 10 th days of dressing change were significantly increased (with Z values of -3.12 and -3.50, respectively, P <0.01). Conclusions: Hypochloric acid can kill Escherichia coli both in free and biofilm status. Hypochloric acid at a low concentration shows a rapid bactericidal effect on mature Escherichia coli biofilm, and the higher the concentration of hypochloric acid, the better the bactericidal effect. The hypochloric acid of 100 μg/mL is effective in reducing the bacterial load on wounds with Escherichia coli infection in patients, as evidenced by a reduction in wound exudate and indirect promotion of granulation tissue growth, which is more effective than povidone iodine, the traditional topical antimicrobial agent.

Background: Diabetic foot ulcer (DFU) is the main cause of disability in diabetic patients. However, the molecular changes underlying the occurrence and progression of DFU remain unclear. We conducted this study to examine gene alterations in different DFU patients., Methods: GSE143735 and GSE134431 transcriptome data sets were acquired from the Gene Expression Omnibus database, and differential expression analyses of the genes in these data sets were performed. A functional enrichment analysis of the differentially expressed genes (DEGs) was performed using clusterProfiler package in R. To examine the correlations between DEGs and significant immune-related genes, we identified the intersecting ulcer-related DEGs, healing-related DEGs, and immune-related DEGs. Finally, we further investigate the relationship between the selected genes with immune cell regulation via a single-sample gene set enrichment analysis, and the infiltration of 28 immune cells in common diabetes samples, unhealed DFU samples, and healed samples DFU were compared., Results: We found 238 upregulated genes and 207 downregulated genes in the diabetic foot (DF) patients with ulcers compared to the DF patients without ulcers, and 74 upregulated genes and 28 downregulated genes in the healed samples compared to the unhealed samples. To examine the main biological functions, we conducted a functional enrichment analysis. The results showed that the biological functions of functional enrichment analysis included neutrophil degranulation, leukocyte chemotaxis, myeloid leukocyte migration, phagosome, cytokine-cytokine receptor interaction, and the chemokine signaling pathway. Interleukin (IL)-1B was more highly expressed in patients with ulcers and healed DFU patients than those without ulcers and unhealed DFU patients. Finally, the immune cell abundance difference results showed that activated cluster of differentiation (CD)8 T cells, central memory CD8 T cells, T follicular helper cells, myeloid-derived suppressor cells, natural killer T cells and monocytes were more highly infiltrated in normal diabetes patients and healed DFU patients than unhealed DFU patients. However, no difference was found between DF patients with and without ulcers., Conclusions: IL-1B is an inflammation gene that can be used to assess and regulate DFU progression., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://atm.amegroups.com/article/view/10.21037/atm-22-75/coif). The authors have no conflicts of interest to declare., (2022 Annals of Translational Medicine. All rights reserved.)

Aspartic proteinases are one of the four families of proteinase enzymes that are widely present in living organisms. They are involved in various physiological events, such as protein degradation, development, and host defense. However, the characterization and functional roles of aspartic proteinases remain to be elucidated in crustaceans. Here, we characterized a fragment of cathepsin D-like cDNA from red swamp crayfish, Procambarus clarkii ( Pc-cathepsin D-like ). The open reading frame of the Pc-cathepsin D-like gene contained 1152 bp, encoding a protein of 383 amino acid residues. We also evaluated the immunological role of the Pc-cathepsin D-like gene in vivo. Spatial distribution analysis revealed that the Pc-cathepsin D-like mRNA was high in the hepatopancreas, followed by the gut, gills, and hemocytes of P. clarkii . The expression levels of the Pc-cathepsin D-like gene increased following challenge with viral (polyinosinic: polycytidylic acid) and bacterial (lipopolysaccharides, peptidoglycan) PAMPs compared with PBS injection. The suppression of the Pc-cathepsin D-like gene by RNA interference significantly increased the expression of immune-associated genes. These results showed that the Pc-cathepsin D-like gene has an essential biological role in innate immune responses because it regulates the expression of immune-associated genes.

Background: The most widely used frailty phenotype and frailty indexes are either time-consuming or complicated, thus restricting their generalization in clinical practice; and therefore, an easier and faster screening tool is needed to be developed., Objective: To select sensitive symptoms in traditional Chinese medicine (TCM) and study whether they can improve the risk prediction of frailty., Methods: This is a cross-sectional study enrolling 2249 Chinese elderly community dwellers. Data were collected via face-to-face inquiries, anthropometric measurements, laboratory tests, and community health files. Frailty was the main outcome measure, and it was evaluated by Fried's frailty phenotype (FP). The ordinal logistic regression model was used to identify the factors associated with frailty. The risk assessment plot was used to compare the discriminative ability for frailty among models with and without TCM symptoms., Results: The identified sensitive influential factors for frailty included age, education level, dietary habits, chronic obstructive pulmonary disease, diabetes, cerebral infarction, osteoporosis, cold limbs, lethargy and laziness in speaking and moving, weakness of lower limbs, slow movement, dry mouth and throat, and glazed expression. The risk prediction for "frailty cumulative components ≥1" was not significantly increased, while for "frailty cumulative components ≥2", a new model developed with the above selected TCM symptoms had a higher AUC than the baseline model without it (0.79 VS 0.81, P =0.002). And the NRI and IDI for the new model were 41.4% ( P =0.016) and 0.024% ( P =0.041), respectively., Conclusion: This research might provide an easier and faster way for early identification and risk prediction of frailty in elderly community dwellers., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2021 Zhen Qi et al.)

Polycystic ovary syndrome (PCOS) is a heterogeneous disorder with evidence of polygenetic components, and obesity may be a risk factor for hyperandrogenism. Previous studies have shown that LHCGR is enriched in the ovary and LHCGR deficiency causes infertility without typical PCOS phenotypes. ALMS1 is implicated in obesity and hyperandrogenism, the common phenotypes among PCOS patients. Through whole-exome sequencing of 22 PCOS families and targeted candidate gene sequencing of additional 65 sporadic PCOS patients, we identified potential causative mutations in LHCGR and ALMS1 in a sibling-pair PCOS family and three sporadic PCOS patients. The expression of LHCGR L638P in granulosa-like tumor cell line (KGN) cells promoted cyclic adenosine monophosphate production and granulosa cell proliferation, indicating that LHCGR L638P is an activating mutation. Lhcgr L642P/L642P mice showed an irregular estrous cycle, reduced follicles with dynamic folliculogenesis, and increased testosterone (T), estradiol (E2), and dehydroepiandrosterone. Lhcgr +/L642P Alms1 +/PB mice displayed increased T and E2 but decreased late secondary and preovulatory follicles. We showed that activating mutation of LHCGR likely plays important roles in the pathophysiology of PCOS involving abnormal reproductive physiology, whereas ALMS1 deficiency may promote anovulatory infertility via elevated androgens, suggesting that the disturbed LHCGR and ALMS1 cooperatively induce PCOS phenotypes, characterized as anovulation and hyperandrogenemia frequently observed in PCOS patients with obesity., (Copyright © 2021 Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, and Genetics Society of China. Published by Elsevier Ltd. All rights reserved.)

The quantum anomalous Hall effect (QAHE), carrying dissipationless chiral edge states, occurs without any magnetic field. Two main strategies were proposed to host QAHE: the magnetic topological insulator thin films and graphene systems. Only the former one was realized in experiment at low temperature. In this paper, by dealing with the two-dimensional electron gas with an anti-dot lattice, a realistic platform is proposed to host the QAHE with both Chern number [Formula: see text] and [Formula: see text]. Based on the calculation of the Berry curvature integral and spacial wave function, the topological nature of the QAH edge states is well demonstrated. In the QAH region, the conductance shows quantized plateaus and their values are robust against Anderson disorder. In addition, we have also studied the effects of the size and shape of the anti-dot lattice on QAHE and they provide extra manners to adjust the system parameters. Taking the advantages of the well developed micro-manufacture technique in semiconductors, the proposal is experimentally accessible in micro-scale.

G protein-coupled receptors (GPCRs) play important roles in human physiology. GPCRs are involved in immunoregulation including regulation of the inflammatory response. Chemotaxis of phagocytes and lymphocytes is mediated to a great extent by the GPCRs for chemoattractants including myriads of chemokines. Accumulation and activation of phagocytes at the site of inflammation contribute to local inflammatory response. A handful of GPCRs have been found to transduce anti-inflammatory signals that promote resolution of inflammation. These GPCRs interact with selected metabolites of arachdonic acid, such as lipoxins, and of omega-3 essential fatty acids, such as resolvins and protectins. Despite mounting evidence for the in vivo functions of these anti-inflammatory and pro-resolving ligands paired with their respective GPCRs, the underlying signaling mechanisms have not been fully delineated. The present review summarizes what we have learned about these GPCRs, their structures and signaling pathways and the prospect of targeting these receptors for novel anti-inflammatory therapies.

Objective: To explore the effects of acute paraquat poisoning on cognitive function of patients through neuropsychologic test. Methods: In June 2019, 36 patients with acute paraquat poisoning in the emergency department of a provincial hospital in Hebei Province were selected as the case group. 36 healthy individuals were selected as control group. The cognitive function and depressive state were assessed by mini mental state scale, auditory word learning test, digit span test, connection test, Boston Naming Test and geriatric depression scale. Results: The results of Mini-Mental State examination showed that the total score of the case group was lower than that of the control group, the difference was statistically significant ( P <0.05) . The results of the Auditory Vocabulary Learning test showed that the scores of delayed recall, clue recall, corrective ability and semantic learning strategies of the case group were significantly lower than those in the control group ( P <0.05) . There was no significant difference in the scores of immediate memory between the two groups ( P >0.05) . The scores of Digit Span test and Boston Naming test in the control group were higher than those in the case group, the Trail Making test time in the control group was shorter than that in the case group, and the differences were statistically significant ( P <0.05) . Conclusion: Acute paraquat poisoning can impair human cognitive ability to a certain extent.

With landsat-series multi-temporal image data, percentage of vegetation cover (PVC) was estimated by pixel dichotomy. The linear regression analysis and center of gravity migration methods were used to explore the characteristics of the spatiotemporal changes of vegetation cover in Shenzhen from 2000 to 2018. The CA-Markov model was combined to predict future land cover in Shenzhen. The results showed that the PVC in Shenzhen demonstrated obvious regional differentiation characteristics from 2000 to 2018. The eastern region occupied larger proportion than the wes-tern part, while the southern region was larger than the north part. This feature exhibited good consistency with regional topographic effect. The spatial migration characteristic of the center of gravity of PVC was from northwest to southeast, and then from southeast to northwest, with a migration rate of 551.2 m·a -1 . This process was closely related to urbanization in Shenzhen. The PVC in Shen-zhen tended to be generally improved from 2000-2018, with a improvement rate of 0.005·a -1 . The percentage of significantly improved and degraded PVC area was 30.8% and 12.8%, respectively. The CA-Markov method was used to predict the land cover/use pattern of Shenzhen in 2024 under two scenarios, theoretical scenario and natural scenario. There was no significant difference in proportion of the area of the land cover/use patterns obtained by the two kinds of prediction method, with the difference threshold being 0-1.2%. Compared with the data before 2018, the proportion of arbor forests and arable land converted into construction land in Shenzhen would be significantly reduced in 2024, whereas the contradiction between supply and demand would be still tense.

Lysyl oxidase-like 2 (LOXL2) is a member of the lysyl oxidase (LOX) family that contributes to tumor cell metastasis. Our previous data identified two splice variants of LOXL2 (i.e., LOXL2 Δ72 and Δ13) in esophageal squamous cell carcinoma (ESCC) cells that increased cell invasiveness and migration but had lower LOX activities than wild-type LOXL2 (LOXL2 WT). We generated a series of LOXL2 deletion mutants with different deleted biochemical domains and examined the relationship between the cell migration abilities and catalytic activities, as well as subcellular locations, of these deletion mutants compared with LOXL2 WT in ESCC cells to explore the mechanism of LOXL2-driven ESCC cell migration. Our results indicated that the deletion mutants of LOXL2 had impaired deamination enzymatic activity; LOXL2 ΔSRCR4, which lacks the fourth scavenger receptor cysteine-rich (SRCR) domain, had lower enzymatic activity; and LOXL2 Y689F had no catalytic activity compared with LOXL2 WT. However these two mutants stimulated greater cellular migration than LOXL2 WT. Furthermore, the degree of cell migration promoted by LOXL2 ΔLO (in which the LOX-like domain was deleted) was higher than that of LOXL2 WT, and LOXL2 ΔSRCR3, which does not have the third SRCR domain, had lower LOX activity and cellular migration ability than LOXL2 WT. These results suggested that LOXL2 promotes ESCC cell migration independent of catalytic activity., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: Long noncoding RNA MALAT1 is closely related to diabetes and kidney diseases and is expected to be a new target for the diagnosis and treatment of diabetic nephropathy., Objective: This study aimed to explore the circulating expression level and significance of lncRNA Malat1 in patients with type 2 diabetes mellitus (T2DM) and diabetic kidney disease (DKD)., Methods: Quantitative real-time PCR (qPCR) was conducted to assess the expression of lncRNA Malat1 in 20 T2DM patients, 27 DKD patients, and 14 healthy controls, and then, the clinical significance was analyzed., Results: LncRNA MALAT1 expression in peripheral blood mononuclear cells (PBMC) was significantly upregulated in T2DM and DKD groups when compared to control. Pearson's correlation analysis showed correlation of lncRNA MALAT1 levels with ACR, urine β 2-microglobulin ( β 2-MG), urine α 1-microglobulin ( α 1-MG), creatinine (Cr), and glycosylated hemoglobin (HbA1c), while negative with superoxide dismutase (SOD) ( r = -0.388, P < 0.05). Binary regression analysis showed that ACR, creatinine, α 1-MG, and LncRNA Malat1 were the risk factors for diabetic nephropathy with OR value of 1.166, 1.031, 1.031, and 2.019 ( P < 0.05). The area under ROC curve (AUC) of DKD identified by the above indicators was 0.914, 0.643, 0.807, and 0.797, respectively. The AUC of Joint prediction probability of DKD recognition was 0.914, and the sensitivity and specificity of DKD diagnosis were 1.0 and 0.806, respectively. (Take ≥0.251 as the diagnostic cutoff point)., Conclusion: LncRNA Malat1 is highly expressed in DKD patients, and the combined detection of ACR, creatinine, α 1-MG, and LncRNA Malat1 with diabetes mellitus may be the best way to diagnose diabetic nephropathy., Competing Interests: The authors have no conflicts of interest to declare., (Copyright © 2020 Lian-ji Zhou et al.)

Heat shock protein (HSP) is a family of highly conserved protein, which exists widely in various organisms and has a variety of important physiological functions. Currently, there is no systematic analysis of HSPs in human glioma. The aim of this study was to investigate the characteristics of HSPs through constructing protein-protein interaction network (PPIN) considering the expression level of HSPs in glioma. After the identification of the differentially expressed HSPs in glioma tissues, a specific PPIN was constructed and found that there were many interactions between the differentially expressed HSPs in glioma. Subcellular localization analysis shows that HSPs and their interacting proteins distribute from the cell membrane to the nucleus in a multilayer structure. By functional enrichment analysis, gene ontology analysis, and Kyoto Encyclopedia of Genes and Genomes pathway analysis, the potential function of HSPs and two meaningful enrichment pathways was revealed. In addition, nine HSPs (DNAJA4, DNAJC6, DNAJC12, HSPA6, HSP90B1, DNAJB1, DNAJB6, DNAJC10, and SERPINH1) are prognostic markers for human brain glioma. These analyses provide a full view of HSPs about their expression, biological process, as well as clinical significance in glioma.

To compare clinical and imaging features between patients with an initial negative reverse-transcription-polymerase chain-reaction (RT-PCR) test and patients with an initial positive RT-PCR test. CT follow-up analysis in the negative RT-PCR group is also described.Thirty-three patients with SARS-CoV-2 infection confirmed by RT-PCR, with 216 lesions upon CT, were included. Demographic information and chest CT imaging features were collected.The average age in the whole study group was 46.9 ± 11.1 years, with 18 males and 15 females. Patients in the positive RT-PCR test group were more likely to have a fever than patients in the negative RT-PCR test group (85.7% vs 50%, P < .05). Lesions in the positive group were more likely to be located in the peripheral area than lesions in the negative group (83.6% vs 68.2%, P < .05). Regarding the appearance of 216 lesions, ground-glass opacities (GGOs) with consolidation (43.2%) was the most common appearance in the negative group, followed by pure GGOs (31.8%), while in the positive group, pure GGOs (32%) and GGOs with interlobular septal thickening (32.8%) were both most frequent, and the difference between them was evident (P < .05). For the follow-up analysis, the largest short-axis of a lesion was smaller upon follow-up (median size 13.6 mm vs 14 mm), albeit by a smaller margin. Pure GGOs decreased in frequency, from 31.3% to 21.3%, while consolidation increased in frequency, from 7.5% to 12.5%.The manifestations of COVID-19 in patients with a first negative RT-PCR test and patients with a positive first RT-PCR test are different to some extent. The consolidation component may increase after follow-up.

Cathepsins are a group of lysosomal hydrolytic enzymes, broadly distributed in animals, and regulate various physiological processes. However, the immune functions of cathepsins are poorly understood in invertebrates. Therefore, to further provide information about the importance of cathepsins in the innate immune system of crustaceans, cathepsin A from Procambarus clarkii (Pc-cathepsin A) was characterized and its distribution in different tissues was determined. The immunological functions of the Pc-cathepsin A were also evaluated. The Pc-cathepsin A showed high sequence homology to cathepsins of other species, as it contained serine and histidine active sites. Quantitative RT-PCR analysis revealed that the expression of Pc-cathepsin A was highest in the gill, gut, and the hepatopancreas, with variable amounts in the muscle, stomach, heart, and hemocytes. The mRNA expression of Pc-cathepsin A was significantly increased in hepatopancreas challenged with lipopolysaccharide (LPS), peptidoglycan (PGN), and polycytidylic acid (poly I:C). The results of an in vivo analysis revealed that Pc-cathepsin A knockdown by double-stranded RNA in P. clarkii modulated the expression of immune-pathway associated genes in hepatopancreas. Collectively, these results suggest that Pc-cathepsin A modulates innate immune responses by affecting the expression of immune-pathway associated genes, thus revealing a regulatory link between Pc-cathepsin A and immune pathways in P. clarkii, and that Pc-cathepsin A plays an essential biological role in the immune defence against microbial pathogens., Competing Interests: Declaration of competing interest Authors declare that they have no conflict of interest., (Copyright © 2020. Published by Elsevier B.V.)

Alloys with ultra-high strength and sufficient ductility are highly desired for modern engineering applications but difficult to develop. Here we report that, by a careful controlling alloy composition, thermomechanical process, and microstructural feature, a Co-Cr-Ni-based medium-entropy alloy (MEA) with a dual heterogeneous structure of both matrix and precipitates can be designed to provide an ultra-high tensile strength of 2.2 GPa and uniform elongation of 13% at ambient temperature, properties that are much improved over their counterparts without the heterogeneous structure. Electron microscopy characterizations reveal that the dual heterogeneous structures are composed of a heterogeneous matrix with both coarse grains (10∼30 μm) and ultra-fine grains (0.5∼2 μm), together with heterogeneous L1 2 -structured nanoprecipitates ranging from several to hundreds of nanometers. The heterogeneous L1 2 nanoprecipitates are fully coherent with the matrix, minimizing the elastic misfit strain of interfaces, relieving the stress concentration during deformation, and playing an active role in enhanced ductility.

Periodontal diseases are infectious diseases that are characterized by progressive damage to dental support tissue. The major goal of periodontal therapy is to regenerate the periodontium destroyed by periodontal diseases. Human periodontal ligament (PDL) tissue possesses periodontal regenerative properties, and periodontal ligament stem cells (PDLSCs) with the capacity for osteogenic differentiation show strong potential in clinical application for periodontium repair and regeneration. Noncoding RNAs (ncRNAs), which include a substantial portion of poly-A tail mature RNAs, are considered "transcriptional noise." Recent studies show that ncRNAs play a major role in PDLSC differentiation; therefore, exploring how ncRNAs participate in the osteogenic differentiation of PDLSCs may help to elucidate the underlying mechanism of the osteogenic differentiation of PDLSCs and further shed light on the potential of stem cell transplantation for periodontium regeneration. In this review paper, we discuss the history of PDLSC research and highlight the regulatory mechanism of ncRNAs in the osteogenic differentiation of PDLSCs., Competing Interests: Conflict-of-interest statement: The authors declare that they have no conflict of interest., (©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.)

Objective: To compare the von Mises stresses of the pedicle screw system and the displacement of injured vertebrae using 3-D finite element analysis, and to evaluate the curative effect of the pedicle screw system., Methods: Finite element methods were used for biomechanical comparison of four posterior short segment pedicle screw fixation techniques. The different pedicle screw models are traditional trajectory (TT), Universal Spine System (USS), cortical bone trajectory (CBT), and CBT at the cranial level and pedicle screw (PS) at the caudal level (UP-CBT). The stress distribution of the screws and connecting rods under different working conditions and the displacement of the injured vertebrae were compared and analyzed., Results: After the pedicle screw system was fixed, the stress under vertical compression was mainly concentrated at the proximal end of the screw, while the stress was mainly concentrated on the connecting rod during flexion, extension, lateral flexion, and rotation. The TT group had the greatest stress during the flexion, extension, and left and right rotation. The UP-CBT group was most stressed when the left and right sides were flexed; the stress of the USS screw system was less than that of the other three models during flexion, lateral flexion, and rotation. The maximum von Mises stress values of pedicle screws in all exercise states were 556.2, 340.7, 458.1, and 533.4 MPa, respectively. In the USS group, the displacement of the injured vertebra was small in the flexion, and the left and right lateral flexion and the right rotation were higher than in the TT group and the CBT group. The maximum displacements of the injured vertebrae in all motion states were 1.679, 1.604, 1.752, and 1.777 mm, respectively., Conclusion: Universal Spine System pedicle screws are relatively less stressed under different working conditions, the risk of breakage is small, and the model is relatively stable; CBT screws do not exhibit better mechanical properties than conventional pedicle screws and USS pedicle screws., (© 2020 The Authors. Orthopaedic Surgery published by Chinese Orthopaedic Association and John Wiley & Sons Australia, Ltd.)

Nanometer zinc oxide has become a new hotspot in the research of tissue engineering materials due to its excellent antibacterial properties, biocompatibility, and anti-tumor properties. In this paper, the existing research results were summarized, generalized, and analyzed. The antibacterial mechanism of nanometer zinc oxide was discussed in depth. The antibacterial properties and advantages of the latest nanometer zinc oxide composite materials were introduced in detail. In this review, we made prospect of the future application of nanometer zinc oxide.

A cesium bismuth germanate, Cs 2 Bi 2 O(Ge 2 O 7 ) (CBGO), was synthesized by a traditional high-temperature solid-state reaction. Its structure features a 3D network composed of a 1D chains composed of Bi 2 O 8 dimers that are further bridged by Ge 2 O 7 dimers, forming tunnels of seven member rings (MRs) that are filled by the Cs + cations. CBGO exhibits extraordinary larger second harmonic generation (SHG) response of about 13.7 times that of KDP (KH 2 PO 4 ) under 1064 nm laser radiation and 1.1 times that of KTP (KTiOPO 4 ) under 2.05 μm laser radiation, which is the highest among all of the metal germanates reported so far. CBGO possesses a moderate birefringence (0.073 at 1064 nm) and is phase matchable. Furthermore, CBGO melts congruently and exhibits high thermal stability., (© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Dendrobium devonianum has been used as herbal medicines and nutraceutical products since ancient time in China. However, its chemical composition and pharmacological mechanisms are not fully known. In present studies, by chemical purification and characteristic identification, we discovered a novel polysaccharide from D. devonianum, which was designated as DvP-1 with molecular weights of 9.52 × 10 4  Da. DvP-1 is a homogeneous heteropolysaccharide consisting of D-mannose and d-glucose in the molar ration of 10.11: 1. The main glycosidic linkages were β-1, 4-Manp, which were substituted with acetyl groups at the O-2, O-3 and/or O-6 positions. DvP-1 was found to directly stimulate the activation of macrophages in vitro, as evidenced by inducing morphologic change, thereby promoting the production of cytokines TNF-α, IL-6 and NO, and enhancing the pinocytic activity of macrophages. By establishing a zebrafish model, we also found that DvP-1 could alleviate vinorelbine-induced decrease of macrophages in vivo. Further findings indicated that DvP-1 activated macrophages through several toll-like receptors (TLRs), but mainly through TLR4. DvP-1 served as a TLR4 agonist and induced ERK, JNK, p38, and IκB-α phosphorylation, suggesting the activation of MAPK and NFκB signaling pathways downstream of TLR4. These findings could help us further understand the immunomodulating effects of D. devonianum in Chinese medicines or health foods for immunocompromised persons. They also show the medicinal value of DvP-1 for the treatment of cancer and infectious diseases caused by TLR4 dysfunction., (Copyright © 2019 Elsevier B.V. All rights reserved.)

A new ultraviolet nonlinear optical material, namely LiHgPO 4 , was synthesized using the mild hydrothermal method. The structure of LiHgPO 4 features novel double layers constructed by severely distorted HgO 6 octahedra and PO 4 tetrahedra, which are further interconnected by LiO 4 tetrahedra to form a three-dimensional structure. LiHgPO 4 exhibits a very strong second harmonic generation (SHG) response of 11.0 times that of KH 2 PO 4 and a relatively large birefringence (0.068 at 1064 nm) among the reported SHG-active phosphates. Theoretical calculations revealed that the introduction of the Hg 2+ in a highly distorted HgO 6 octahedral geometry is crucial to produce the strong SHG response and large birefringence.

By using hydrofluoric acid as a solubilizer, the first alkali-metal niobium iodate and an alkali-earth metal niobium iodate, i.e. (H3O)HCs2Nb(IO3)9 and SrNbO(IO3)5, have been obtained. An obvious cation-controlled polarity shift is observed in the Ae/A-Nb5+-IO3 system. (H3O)HCs2Nb(IO3)9 gives a strong second harmonic generation (SHG) signal about 6 times that of KH2PO4 (KDP), making it a promising nonlinear optical (NLO) material.